Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Pembrolizumab

Tin Fluorides

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 40 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 60 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib at the RP2D orally once daily for up to 35 cycles, until disease progression, unacceptable toxicity, or consent withdrawal. All participants who stop pembrolizumab after 35 cycles with SD or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping pembrolizumab from the initial treatment phase.

Pharmaceutical form: tablets Route of administration: oral

Cabozantinib

Pharmaceutical form: solution Route of administration: injection

Elaine Lam, MD

This is a phase I/II open-label study designed to evaluate the combination of pembrolizumab and cabozantinib in subjects with locally advanced, recurrent, or metastatic renal cell carcinoma. Sequential dose escalation of cabozantinib with standard dose pembrolizumab will occur in the phase I dose escalation part of the study to determine the recommended phase 2 dose (RP2D). Subsequently, subjects will receive cabozantinib at the RP2D in combination with pembrolizumab in the phase II dose expansion part of the study.

Primary Objectives

* To determine the efficacy based on objective response rate \[ORR = complete response (CR) + partial response (PR)\] of pembrolizumab and cabozantinib when administered in combination in subjects with locally advanced or metastatic renal cell carcinoma..

Secondary Objectives

* To characterize dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) for the combination.
* To assess other measures of anti-tumor activity of the combination of pembrolizumab and cabozantinib in subjects with locally advanced or metastatic renal cell carcinoma.

Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

Phase I/II Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

Measured through the complete response (CR) + partial response (PR)\] of pembrolizumab and cabozantinib when administered in combination in subjects with locally advanced or metastatic renal cell carcinoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

* The MTD is defined as the highest dose level with no more than 1 DLT reported in 6 DLT-evaluable subjects.
* The Recommended Phase 2 Dose (RP2D) of cabozantinib will be selected based on the clinical data and will not exceed the MTD. If \< 2/6 subjects experience a DLT at 60 mg daily during dose escalation, then 60 mg daily will be considered the RP2D. If ≥ 2/6 subjects experience DLTs at 60 mg daily, and ≤ 1/6 subjects experience a DLT at 40 mg daily, then 40 mg daily will be considered the RP2D. The dose of pembrolizumab will be constant at 200 mg IV every 3 weeks.

Assessed through Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Dose Limiting Toxicity (DLT) was defined as any of the following events occurring during the DLT assessment window (21 days) and is assessed by the investigator to be likely related to study treatment (pembrolizumab and/or cabozantinib).

* Grade ≥ 3 non-hematologic, non-hepatic adverse events
* Grade 3 nausea, vomiting, or diarrhea lasting \>72 hours despite maximal medical therapy.
* Grade ≥ 4 neutropenia (ANC \< 500 cells/μL) lasting \> 7 days
* Grade ≥ 3 febrile neutropenia
* Grade ≥ 4 anemia
* Grade ≥ 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with clinically significant bleeding
* Grade ≥ 3 elevation of serum hepatic transaminase (ALT or AST).
* Grade ≥ 3 elevation of serum total bilirubin.
* ALT or AST \> 3 × upper limit of normal (ULN) AND total bilirubin \>2 × ULN will require permanent treatment discontinuation.

Measured as the time it takes for an occurrence of documented disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Measured as the time it takes for an occurrence of death due to any cause

DCR is the sum of the complete response, partial response, and stable disease rates

Duration of time that patients maintain RECIST response to treatment

Merck Sharp & Dohme LLC

University of Colorado, Denver

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 40 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Cabozantinib: Pharmaceutical form: tablets Route of administration: oral

Pembrolizumab: Pharmaceutical form: solution Route of administration: injection

Phase 1: Pembrolizumab 200 mg Plus Cabozantinib 40mg

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 60 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Cabozantinib: Pharmaceutical form: tablets Route of administration: oral

Pembrolizumab: Pharmaceutical form: solution Route of administration: injection

Phase 1: Pembrolizumab 200 mg Plus Cabozantinib 60mg

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib at the RP2D orally once daily for up to 35 cycles, until disease progression, unacceptable toxicity, or consent withdrawal. All participants who stop pembrolizumab after 35 cycles with SD or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping pembrolizumab from the initial treatment phase.

Cabozantinib: Pharmaceutical form: tablets Route of administration: oral

Pembrolizumab: Pharmaceutical form: solution Route of administration: injection

Phase 2: Pembrolizumab 200 mg Plus Cabozantinib at the RP2D

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Elaine Lam

Phase 1/2: All Evaluable Patients Treated at Pembrolizumab 200 mg IV Q3W + Cabozantinib 60 mg PO QD

Phase 1 Dose Escalation Cohort: Pembrolizumab 200 mg IV Q3W Plus Cabozantinib 40mg PO QD

Total RCC patients who were evaluable for response at the dose level

Efficacy of Pembrolizumab and Cabozantinib Based on Objective Response Rate

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 40 mg or 60 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Cabozantinib: Pharmaceutical form: tablets Route of administration: oral

Pembrolizumab: Pharmaceutical form: solution Route of administration: injection

Phase 1: Pembrolizumab 200 mg IV Q3W Plus Cabozantinib 40mg or 60 mg PO QD

There were 8 total patients enrolled in phase I cohorts of the study (5 in cohort 1 (PEM 200/CABO 40) and 3 in cohort 2 (PEM 200/CABO 60). Among the 5 patients in cohort 1, only 3 were evaluable for DLT and MTD. In total, 6 patients in phase I were evaluable for DLT and MTD.

Maximally Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Phase 1 Cohort 1: Pembrolizumab 200 mg Plus Cabozantinib 40mg

Phase 1 Cohort 2: Pembrolizumab 200 mg Plus Cabozantinib 60mg

Total patients enrolled in phase I of the study who were evaluable for DLTs.

Dose Limiting Toxicities

All Patients Treated at the RP2D of Pembrolizumab 200 mg IM Q3W Plus Cabozantinib 60 mg PO QD

All 40 patients treated at the RP2D were included in the survival analyses.

Progression-Free Survival

Overall Survival

All Evaluable Patients Treated at Pembrolizumab 200 mg IV Q3W + Cabozantinib 60 mg PO QD

Disease Control Rate (DCR), AKA Clinical Benefit Rate (CBR)

All patients evaluable for response at the RP2D of Pembrolizumab 200 mg IM Q3W plus Cabozantinib 60 mg PO QD

Spots Global Cancer Trial Database for Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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